Full Text:   <2481>

Summary:  <1873>

Suppl. Mater.: 

CLC number: R979.1

On-line Access: 2024-08-27

Received: 2023-10-17

Revision Accepted: 2024-05-08

Crosschecked: 2020-05-26

Cited: 0

Clicked: 4365

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Xi-Ping Zhang

https://orcid.org/0000-0002-3556-9681

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2020 Vol.21 No.6 P.495-508

http://doi.org/10.1631/jzus.B1900584


Screening of miRNAs associated with lymph node metastasis in Her-2-positive breast cancer and their relationship with prognosis


Author(s):  En-Qi Qiao, Hong-Jian Yang, Xi-Ping Zhang

Affiliation(s):  Department of Breast Surgery, Cancer Hospital of University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou 310022, China

Corresponding email(s):   zxp99688@sina.com

Key Words:  Breast cancer (BC), Human epidermal growth factor receptor 2 (Her-2), Lymphatic metastasis, MicroRNA (miRNA), Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)


Share this article to: More <<< Previous Article|

En-Qi Qiao, Hong-Jian Yang, Xi-Ping Zhang. Screening of miRNAs associated with lymph node metastasis in Her-2-positive breast cancer and their relationship with prognosis[J]. Journal of Zhejiang University Science B, 2020, 21(6): 495-508.

@article{title="Screening of miRNAs associated with lymph node metastasis in Her-2-positive breast cancer and their relationship with prognosis",
author="En-Qi Qiao, Hong-Jian Yang, Xi-Ping Zhang",
journal="Journal of Zhejiang University Science B",
volume="21",
number="6",
pages="495-508",
year="2020",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1900584"
}

%0 Journal Article
%T Screening of miRNAs associated with lymph node metastasis in Her-2-positive breast cancer and their relationship with prognosis
%A En-Qi Qiao
%A Hong-Jian Yang
%A Xi-Ping Zhang
%J Journal of Zhejiang University SCIENCE B
%V 21
%N 6
%P 495-508
%@ 1673-1581
%D 2020
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1900584

TY - JOUR
T1 - Screening of miRNAs associated with lymph node metastasis in Her-2-positive breast cancer and their relationship with prognosis
A1 - En-Qi Qiao
A1 - Hong-Jian Yang
A1 - Xi-Ping Zhang
J0 - Journal of Zhejiang University Science B
VL - 21
IS - 6
SP - 495
EP - 508
%@ 1673-1581
Y1 - 2020
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1900584


Abstract: 
The aim of this study was to identify some biomarkers for predicting lymph node metastasis and prognosis of human epidermal growth factor receptor 2 (Her-2)-positive breast cancer (BC). We analyzed correlations between microRNAs (miRNAs) and the prognosis of patients with BC based on data collected from The Cancer Genome Atlas (TCGA) database. The expression levels of miR-455, miR-143, and miR-99a were measured in clinical samples of Her-2-positive BC patients with different degrees of lymph node metastasis. We investigated the impacts of overexpressed miR-455 on the proliferation and invasiveness of MDA-MB-453 cells and measured its effects on the expression of long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of miR-455 was significantly and positively correlated to the prognosis and overall survival (OS) of the BC (P=0.028), according to TCGA information. The expression level of miR-455 was positively correlated with OS and relapse-free survival (RFS) of patients with Her-2-positive BC, and was negatively correlated with the number of metastatic lymph nodes (P<0.05). Transwell assay suggested that MDA-MB-453 cells became much less invasive (P<0.01) after being transfected with miR-455 mimics. During the qRT-PCR, the expression level of MALAT1 declined significantly after transfection (P<0.01). Overexpressed miR-455 significantly inhibited the proliferation and migration of MDA-MB-453 cells and the expression of MALAT1. We conclude that miR-455 may be a useful potential biomarker for forecasting lymph node metastasis and the prognosis of Her-2-positive BC patients. miR-455 may play an important role in lymph node metastasis of BC by interacting with MALAT1.

Her-2阳性乳腺癌淋巴结转移相关的miRNA的筛选及其与患者预后关系的研究

目的:寻找一种或多种能预测人类表皮生长因子受体2(Her-2)阳性乳腺癌患者是否发生淋巴结转移及其预后的分子标志物.
创新点:本研究发现,miR-455与Her-2阳性乳腺癌转移相关,可能是一个预测Her-2阳性乳腺癌患者淋巴结转移和预后的分子标志物.miR-455可以通过与长链非编码RNA人肺腺癌转移相关转录本1(MALAT1)的相互作用,在乳腺癌的淋巴结转移过程中发挥重要功能.
方法:通过下载肿瘤基因组图谱(TCGA)数据库中与乳腺癌相关的微小RNA(miRNA)测序数据,筛选与乳腺癌淋巴结转移相关的miRNA,进一步分析这些miRNA与乳腺癌患者预后的相关性.同时,用实时荧光定量聚合酶链反应(qRT-PCR)方法检测这些miRNA在不同程度淋巴结转移的Her-2阳性乳腺癌患者组织中的表达水平,及其与预后的相关性.通过细胞学实验研究过表达miR-455对Her-2阳性乳腺癌细胞系MDA-MB-453增殖和侵袭能力的影响,并用qRT-PCR检测过表达miR-455对MALAT1表达的影响.
结论:miR-455可能是Her-2阳性乳腺癌患者淋巴结转移和预后的潜在预测因子.

关键词:乳腺癌;人表皮生长因子受体2(Her-2);淋巴结转移;微小RNA(miRNA);人肺腺癌转移相关转录本1(MALAT1)

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Asaduzzaman M, Constantinou S, Min HX, et al., 2017. Tumour suppressor EP300, a modulator of paclitaxel resistance and stemness, is downregulated in metaplastic breast cancer. Breast Cancer Res Treat, 163(3):461-474.

[2]Aversa C, Rossi V, Geuna E, et al., 2014. Metastatic breast cancer subtypes and central nervous system metastases. Breast, 23(5):623-688.

[3]Bartel DP, 2004. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116(2):281-297.

[4]Cao XC, Yu Y, Hou LK, et al., 2016. miR-142-3p inhibits cancer cell proliferation by targeting CDC25C. Cell Prolif, 49(1):58-68.

[5]Chan SH, Huang WC, Chang JW, et al., 2014. MicroRNA-149 targets GIT1 to suppress integrin signaling and breast cancer metastasis. Oncogene, 33(36):4496-4507.

[6]Chang JT, Wang F, Chapin W, et al., 2016. Identification of microRNAs as breast cancer prognosis markers through the Cancer Genome Atlas. PLoS ONE, 11(12):e0168284.

[7]Chen X, Wang YW, Zhu WJ, et al., 2018. A 4-microRNA signature predicts lymph node metastasis and prognosis in breast cancer. Hum Pathol, 76:122-132.

[8]Chiang CH, Chu PY, Hou MF, et al., 2016. MiR-182 promotes proliferation and invasion and elevates the HIF-1α-VEGF-A axis in breast cancer cells by targeting FBXW7. Am J Cancer Res, 6(8):1785-1798.

[9]Chou JJ, Wang BY, Zheng TJ, et al., 2016. MALAT1 induced migration and invasion of human breast cancer cells by competitively binding miR-1 with cdc42. Biochem Biophys Res Commun, 472(1):262-269.

[10]Dong Y, Chang C, Liu J, et al., 2017. Targeting of GIT1 by miR-149* in breast cancer suppresses cell proliferation and metastasis in vitro and tumor growth in vivo. OncoTargets Ther, 10:5873-5882.

[11]Fu XN, Mao X, Wang YX, et al., 2017. Let-7c-5p inhibits cell proliferation and induces cell apoptosis by targeting ERCC6 in breast cancer. Oncol Rep, 38(3):1851-1856.

[12]Gao J, Li LS, Wu MQ, et al., 2013. MiR-26a inhibits proliferation and migration of breast cancer through repression of MCL-1. PLoS ONE, 8(6):e65138.

[13]Guo J, Liu C, Wang W, et al., 2018. Identification of serum miR-1915-3p and miR-455-3p as biomarkers for breast cancer. PLoS ONE, 13(7):e0200716.

[14]Guo LJ, Zhang QY, 2012. Decreased serum miR-181a is a potential new tool for breast cancer screening. Int J Mol Med, 30(3):680-686.

[15]Han YL, Cao XE, Wang JX, et al., 2016. Correlations of microRNA-124a and microRNA-30d with clinicopathological features of breast cancer patients with type 2 diabetes mellitus. SpringerPlus, 5:2107.

[16]He T, Qi FF, Jia L, et al., 2014. MicroRNA-542-3p inhibits tumour angiogenesis by targeting angiopoietin-2. J Pathol, 232(5):499-508.

[17]He T, Qi FF, Jia L, et al., 2015. Tumor cell-secreted angiogenin induces angiogenic activity of endothelial cells by suppressing miR-542-3p. Cancer Lett, 368(1):115-125.

[18]Hirata H, Hinoda Y, Shahryari V, et al., 2015. Long noncoding RNA MALAT1 promotes aggressive renal cell carcinoma through Ezh2 and interacts with miR-205. Cancer Res, 75(7):1322-1331.

[19]Jadaliha M, Zong XY, Malakar P, et al., 2016. Functional and prognostic significance of long non-coding RNA MALAT1 as a metastasis driver in ER negative lymph node negative breast cancer. Oncotarget, 7(26):40418-40436.

[20]https://doi.org/10.18632/oncotarget.9622

[21]Jia XP, Meng LL, Fang JC, et al., 2018. Aberrant expression of miR-142-3p and its target gene HMGA1 and FZD7 in breast cancer and its clinical significance. Clin Lab, 64(6):915-921.

[22]Krell J, Frampton AE, Jacob J, et al., 2012. The clinico-pathologic role of microRNAs miR-9 and miR-151-5p in breast cancer metastasis. Mol Diagn Ther, 16(3):167-172.

[23]Lei R, Tang J, Zhuang X, et al., 2014. Suppression of MIM by microRNA-182 activates RhoA and promotes breast cancer metastasis. Oncogene, 33(10):1287-1296.

[24]Li DG, Xia H, Li ZY, et al., 2015. Identification of novel breast cancer subtype-specific biomarkers by integrating genomics analysis of DNA copy number aberrations and miRNA-mRNA dual expression profiling. Biomed Res Int, 2015:746970.

[25]Li XX, Gao SY, Wang PY, et al., 2015. Reduced expression levels of let-7c in human breast cancer patients. Oncol Lett, 9(3):1207-1212.

[26]Li YY, Kuscu C, Banach A, et al., 2015. miR-181a-5p inhibits cancer cell migration and angiogenesis via downregulation of matrix metalloproteinase-14. Cancer Res, 75(13):2674-2685.

[27]Liu JC, Zhang JK, Li YS, et al., 2016. MiR-455-5p acts as a novel tumor suppressor in gastric cancer by down-regulating RAB18. Gene, 592(2):308-315.

[28]Liu P, Tang HL, Chen B, et al., 2015. miR-26a suppresses tumour proliferation and metastasis by targeting metadherin in triple negative breast cancer. Cancer Lett, 357(1):384-392.

[29]Luan WK, Li LB, Shi Y, et al., 2016. Long non-coding RNA MALAT1 acts as a competing endogenous RNA to promote malignant melanoma growth and metastasis by sponging miR-22. Oncotarget, 7(39):63901-63912.

[30]https://doi.org/10.18632/oncotarget.11564

[31]Markou A, Yousef GM, Stathopoulos E, et al., 2014. Prognostic significance of metastasis-related microRNAs in early breast cancer patients with a long follow-up. Clin Chem, 60(1):197-205.

[32]McGuire A, Brown JAL, Kerin MJ, 2015. Metastatic breast cancer: the potential of miRNA for diagnosis and treatment monitoring. Cancer Metastasis Rev, 34(1):145-155.

[33]M'hamed IF, Privat M, Ponelle F, et al., 2015. Identification of miR-10b, miR-26a, miR-146a and miR-153 as potential triple-negative breast cancer biomarkers. Cell Oncol (Dordr), 38(6):433-442.

[34]Ng EKO, Li R, Shin VY, et al., 2014. MicroRNA-143 is downregulated in breast cancer and regulates DNA methyltransferases 3A in breast cancer cells. Tumour Biol, 35(3):2591-2598.

[35]Pan F, Mao H, Deng L, et al., 2014. Prognostic and clinicopathological significance of microRNA-21 overexpression in breast cancer: a meta-analysis. Int J Clin Exp Pathol, 7(9):5622-5633.

[36]Patel N, Garikapati KR, Ramaiah MJ, et al., 2016. miR-15a/ miR-16 induces mitochondrial dependent apoptosis in breast cancer cells by suppressing oncogene BMI1. Life Sci, 164:60-70.

[37]Pronina IV, Loginov VI, Burdennyy AM, et al., 2017. DNA methylation contributes to deregulation of 12 cancer-associated microRNAs and breast cancer progression. Gene, 604:1-8.

[38]Rinnerthaler G, Hackl H, Gampenrieder SP, et al., 2016. miR-16-5p is a stably-expressed housekeeping microRNA in breast cancer tissues from primary tumors and from metastatic sites. Int J Mol Sci, 17(2):156.

[39]Sakurai M, Miki Y, Masuda M, et al., 2012. LIN28: a regulator of tumor-suppressing activity of let-7 microRNA in human breast cancer. J Steroid Biochem Mol Biol, 131(3-5):101-106.

[40]Salmena L, Poliseno L, Tay Y, et al., 2011. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell, 146(3):353-358.

[41]Schwickert A, Weghake E, Brüggemann K, et al., 2015. MicroRNA miR-142-3p inhibits breast cancer cell invasiveness by synchronous targeting of WASL, integrin alpha V, and additional cytoskeletal elements. PLoS ONE, 10(12):e0143993.

[42]Shiino S, Matsuzaki J, Shimomura A, et al., 2019. Serum miRNA-based prediction of axillary lymph node metastasis in breast cancer. Clin Cancer Res, 25(6):1817-1827.

[43]Singh R, Pochampally R, Watabe K, et al., 2014. Exosome-mediated transfer of miR-10b promotes cell invasion in breast cancer. Mol Cancer, 13:256.

[44]Smeets A, Daemen A, Vanden Bempt I, et al., 2011. Prediction of lymph node involvement in breast cancer from primary tumor tissue using gene expression profiling and miRNAs. Breast Cancer Res Treat, 129(3):767-776.

[45]Sun X, Xu C, Tang SC, et al., 2016. Let-7c blocks estrogen-activated Wnt signaling in induction of self-renewal of breast cancer stem cells. Cancer Gene Ther, 23(4):83-89.

[46]Tavazoie SF, Alarcón C, Oskarsson T, et al., 2008. Endogenous human microRNAs that suppress breast cancer metastasis. Nature, 451(7175):147-152.

[47]Taylor MA, Sossey-Alaoui K, Thompson CL, et al., 2013. TGF-β upregulates miR-181a expression to promote breast cancer metastasis. J Clin Invest, 123(1):150-163.

[48]Venkatadri R, Muni T, Iyer AKV, et al., 2016. Role of apoptosis-related miRNAs in resveratrol-induced breast cancer cell death. Cell Death Dis, 7:e2104.

[49]Vikram R, Ramachandran R, Abdul KSM, 2014. Functional significance of long non-coding RNAs in breast cancer. Breast Cancer, 21(5):515-521.

[50]Volinia S, Croce CM, 2013. Prognostic microRNA/mRNA signature from the integrated analysis of patients with invasive breast cancer. Proc Natl Acad Sci USA, 110(18):7413-7417.

[51]Wang B, Li JD, Sun M, et al., 2014. MiRNA expression in breast cancer varies with lymph node metastasis and other clinicopathologic features. IUBMB Life, 66(5):371-377.

[52]Wang B, Zou AM, Ma LQ, et al., 2017. miR-455 inhibits breast cancer cell proliferation through targeting CDK14. Eur J Pharmacol, 807:138-143.

[53]Wang JL, Sun SJ, Zhang J, et al., 2017. Prognostic value of circulating microRNA-21 for breast cancer: a systematic review and meta-analysis. Artif Cells Nanomed Biotechnol, 45(6):1216-1221.

[54]Wang N, Chen P, Huang LP, et al., 2016. Prognostic significance of microRNA-10b overexpression in breast cancer: a meta-analysis. Genet Mol Res, 15(2):gmr7350.

[55]Wang W, Luo YP, 2015. MicroRNAs in breast cancer: oncogene and tumor suppressors with clinical potential. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 16(1):18-31.

[56]Wang X, Li Y, Qi W, et al., 2015. MicroRNA-99a inhibits tumor aggressive phenotypes through regulating HOXA1 in breast cancer cells. Oncotarget, 6(32):32737-32747.

[57]https://doi.org/10.18632/oncotarget.5355

[58]Weigelt B, Peterse JL, van't Veer LJ, 2005. Breast cancer metastasis: markers and models. Nat Rev Cancer, 5(8):591-602.

[59]Xia M, Li H, Wang JJ, et al., 2016. MiR-99a suppress proliferation, migration and invasion through regulating insulin-like growth factor 1 receptor in breast cancer. Eur Rev Med Pharmacol Sci, 20(9):1755-1763.

[60]Yap YS, Cornelio GH, Devi BCR, et al., 2012. Brain metastases in Asian HER2-positive breast cancer patients: anti-HER2 treatments and their impact on survival. Br J Cancer, 107(7):1075-1082.

[61]Yeh TC, Huang TT, Yeh TS, et al., 2016. miR-151-3p targets TWIST1 to repress migration of human breast cancer cells. PLoS ONE, 11(12):e0168171.

[62]Zhan Y, Li XK, Liang XS, et al., 2017. MicroRNA-182 drives colonization and macroscopic metastasis via targeting its suppressor SNAI1 in breast cancer. Oncotarget, 8(3):4629-4641.

[63]https://doi.org/10.18632/oncotarget.13542

[64]Zhang CF, Liu K, Li T, et al., 2016. miR-21: a gene of dual regulation in breast cancer. Int J Oncol, 48(1):161-172.

[65]Zhang J, Liu Y, 2008. HER2 over-expression and response to different chemotherapy regimens in breast cancer. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 9(1):5-9.

[66]Zhang S, Guo LJ, Zhang G, et al., 2016. Roles of microRNA-124a and microRNA-30d in breast cancer patients with type 2 diabetes mellitus. Tumour Biol, 37(8):11057-11063.

[67]Zhang XP, Chen B, Yang SF, et al., 2018. Roles of MALAT1 in development and migration of triple negative and Her-2 positive breast cancer. Oncotarget, 9(2):2255-2267.

[68]https://doi.org/10.18632/oncotarget.23370

[69]Zhao M, Ding XF, Shen JY, et al., 2017. Use of liposomal doxorubicin for adjuvant chemotherapy of breast cancer in clinical practice. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 18(1):15-26.

[70]Zhou LL, Dong JL, Huang G, et al., 2017. MicroRNA-143 inhibits cell growth by targeting ERK5 and MAP3K7 in breast cancer. Braz J Med Biol Res, 50(8):e5891.

[71]Zhou WB, Zhong CN, Luo XP, et al., 2016. miR-625 suppresses cell proliferation and migration by targeting HMGA1 in breast cancer. Biochem Biophys Res Commun, 470(4):838-844.

[72]List of electronic supplementary materials

[73]Table S1 Primer information of qRT-PCR

[74]Table S2 Sequence information of miRNA mimics

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE